A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence

NCT ID: NCT02061293

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2021-07-30

Brief Summary

Several lines of evidence suggest that classic hallucinogens such as psilocybin can facilitate behavior change in addictions such as alcohol dependence. The proposed investigation is a multi-site, double-blind active-controlled trial (n = 180, 90 per group) contrasting the acute and persisting effects of psilocybin to those of diphenhydramine in the context of outpatient alcoholism treatment.

Detailed Description

Two to four sites will participate in this study. Aims of the study are 1) to characterize the acute effects of PO psilocybin 25 mg/70 kg, 30 mg/70 kg, and 40 mg/70 kg in alcohol dependent patients; 2) to evaluate the effect of psilocybin treatment on drinking outcomes for 32 weeks after the first administration, relative to diphenhydramine control; 3) to test whether or not characteristics of the drug administration session experiences mediate effects of psilocybin on short-term (1 week) persisting effects and post-session drinking behavior, 4) to evaluate the explanatory value of changes in alcohol craving, self-efficacy, motivation, and other psychological domains in accounting for the observed experimental effect of psilocybin relative to diphenhydramine control, and 5) to evaluate pre-post changes in drinking in participants after they receive psilocybin in the third session.

The total duration of psychosocial treatment in the double-blind period will be 12 weeks, and double-blind drug administration sessions will occur after 4 and 8 weeks. In the first psilocybin session, a dose of 25 mg/70 kg will be administered. Depending on the response in the first session, the dose for the second session may be increased to 30 mg/70 kg or 40 mg/70 kg, or held at 25mg/70kg. The dose of diphenhydramine will start at 50 mg, and may be increased to 100 mg or held at 50 mg in the second session, depending on response in the first session. Following completion of the double-blind period (34 weeks after randomization) all participants who meet interim safety criteria will be offered an additional session in which psilocybin will be administered. The drug will be administered during 8-hour sessions in an outpatient setting under close medical and psychiatric monitoring. The drug administration sessions will occur in the context of an extended version of Motivational Enhancement Therapy (Motivational Enhancement and Taking Action, META) with the addition of standardized preparation before and debriefing and follow-up after the psilocybin administration sessions. Extensive screening and baseline assessment will be completed, including thorough safety screening and assessment of participant characteristics that could potentially moderate treatment response. Within-session and short-term persisting effects will be assessed. Drinking outcomes and changes in several potential mediators of treatment effect, including motivation, self-efficacy, craving, depression, anxiety, and spiritual dimensions of the experience, will be measured until 50 weeks after the first drug administration session, for a total of 54 weeks from the initiation of treatment.

Conditions

Alcohol Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Psilocybin

Psilocybin 25 mg/70 kg PO administered at week 4, 25-40 mg/70 kg PO administered at week 8.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Motivational Enhancement and Taking Action (META)

Intervention Type: BEHAVIORAL

Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.

Diphenhydramine

Diphenhydramine 50 mg PO administered at week 4, 50-100 mg PO administered at week 8.

Group Type: ACTIVE_COMPARATOR

Diphenhydramine

Intervention Type: DRUG

Motivational Enhancement and Taking Action (META)

Intervention Type: BEHAVIORAL

Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.

Interventions

Psilocybin

Intervention Type: DRUG

Diphenhydramine

Intervention Type: DRUG

Motivational Enhancement and Taking Action (META)

Manualized psychosocial intervention based on motivational enhancement therapy, functional analysis, and implementation of a change plan.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. Males and females age 25-65 with SCID (DSM-IV) diagnosis of alcohol dependence who

2. Want to stop or decrease their drinking

3. Are not participating in any formal treatment for alcohol dependence (12-step meetings are not considered treatment)

4. Are able to provide voluntary informed consent

5. Have at least 4 heavy drinking days in the past 30 days

6. If female of childbearing potential, are willing to use approved form of contraception from screening until after the psilocybin administration sessions

7. Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions

8. Are able to provide adequate locator information.

Exclusion Criteria

1. Medical conditions that would preclude safe participation in the trial (e.g., seizure disorder, significantly impaired liver function, coronary artery disease, heart failure, uncontrolled hypertension (above 165/95 mmHg at screening), history of cerebrovascular accident, asthma, hyperthyroidism, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladder-neck obstruction)

2. Exclusionary psychiatric conditions (schizophrenia, schizoaffective disorder, bipolar disorder, current major depressive episode, current post-traumatic stress disorder, current suicidality or history of medically serious suicide attempt)

3. Cognitive impairment (Folstein Mini Mental State Exam score < 26)

4. A family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives)

5. History of hallucinogen use disorder, or any use in the past 1 year, or >25 lifetime uses;

6. Cocaine, psychostimulant, opioid, or cannabis dependence (past 12 months)

7. Current non-medical use of cocaine, psychostimulants, or opioids (past 30 days)

8. Significant alcohol withdrawal (CIWA-Ar score greater than 7. Patients presenting at screening in withdrawal may be referred for detoxification and reassessed within 30 days)

9. Serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QTc prolongation [QTc > .045 for men, QTc > .047 for women])

10. Serious abnormalities of complete blood count or chemistries

11. Active legal problems with the potential to result in incarceration

12. Pregnancy or lactation

13. Need to take medication with significant potential to interact with study medications (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants).

14. Allergy or hypersensitivity to psilocybin or diphenhydramine.

15. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support).

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heffter Research Institute

OTHER

Sponsor Role: collaborator

University of New Mexico

OTHER

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael P Bogenschutz, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States

Clinical and Translational Science Institute, NYU Langone Medical Center

New York, New York, United States

Countries

United States

References

Pagni BA, Petridis PD, Podrebarac SK, Grinband J, Claus ED, Bogenschutz MP. Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study. Sci Rep. 2024 Feb 7;14(1):3159. doi: 10.1038/s41598-024-52967-8.

Reference Type: DERIVED

PMID: 38326432 (View on PubMed)

Agin-Liebes G, Nielson EM, Zingman M, Kim K, Haas A, Owens LT, Rogers U, Bogenschutz M. Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis. Psychol Addict Behav. 2024 Feb;38(1):101-113. doi: 10.1037/adb0000935. Epub 2023 Jun 5.

Reference Type: DERIVED

PMID: 37276086 (View on PubMed)

O'Donnell KC, Mennenga SE, Owens LT, Podrebarac SK, Baron T, Rotrosen J, Ross S, Forcehimes AA, Bogenschutz MP. Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial. Contemp Clin Trials. 2022 Dec;123:106976. doi: 10.1016/j.cct.2022.106976. Epub 2022 Nov 2.

Reference Type: DERIVED

PMID: 36332827 (View on PubMed)

Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Oct 1;79(10):953-962. doi: 10.1001/jamapsychiatry.2022.2096.

Reference Type: DERIVED

PMID: 36001306 (View on PubMed)

Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PC, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015 Mar;29(3):289-99. doi: 10.1177/0269881114565144. Epub 2015 Jan 13.

Reference Type: DERIVED

PMID: 25586396 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Heffter 113080-2

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

14-00614

Identifier Type: -

Identifier Source: org_study_id